Of the 6 randomized trials in the 1970s-1980s that posed similar questions, the NCI trial was unique in that all patients underwent CT simulation with dose inhomogeneity corrections

Of note, all node positive patients (40%) received chemotherapy with adriamycin and cytoxan for 6-11 cycles. Tamoxifen was added for postmenopausal patients in 1985.

In the MRM patients, there were 63/116 deaths. In the BCT arm, there were 76/121 deaths, 43.8% vs. 37.9% alive at 25.7 yrs with p=0.38. Prior to 25 years, the curves were superimposable but then they began to separate. Thus, the question arose if the treatment toxicity might be causing separation of the curves (Simone NL, et al. Breast Cancer Res Treat. 2012;132(1):197-203.

There are conflicting data regarding cardiovascular complications following breast RT. Some studies report increased cardiac morbidity with left breast radiation. However, many of these positive studies used two-dimensional planning only, and patients were treated prior to the CT planning era.

This study conducted further investigation into the patients treated on the NCI Breast Conservation trial.

Materials and Methods

Approximately half of patients were willing to return to the NCI, and a total of 50/102 (26 BCT, 24 MRM) returned for comprehensive follow-up conducted as follows:

Results

Patient characteristics compared between MRM and BCT patients as well as right breast versus left breast patients were well-balanced with regard to age at diagnosis, current age, BMI, smoking history, hormone replacement, therapy, hypertension, hyperlipidemia, chemotherapy, history of MI, history of heart failure, history of cardiac catheterization or CABG. There was a non-significant trend towards a higher percentage of patients with diabetes in the MRM cohort than the BCT cohort (13 vs 4%).

Central lung distance was <2 cm in 11% (15% right vs. 9% left), 2-3 cm in 50% (53% right vs 46% left), and >3 cm in 39% (35% right vs. 45% left). There were no significant differences in CLD in right versus left.

Exam and laboratory findings were similar between MRM and BCT as well as right versus left with regard to diastolic BP, creatinine, total cholesterol, LDL cholesterol, HDL cholesterol, HbA1c, hs-CRP, proBNP, homocysteine, cystatin-c, Framingham Risk Score. There was a trend toward higher systolic BP in MRM than BCT patients (139 vs. 127). There was also a non-significant trend in pro-BNP in MRM versus BCT (256 vs. 176) and in right than left breast cancer patients (216 vs. 113).

There was no significant increase but there was a trend in the risk of visible atherosclerosis with chemotherapy (HR 2.4, 95% CI 0.94-6.32, p=0.07).

Author's Conclusions

This is the first study reporting comprehensive long-term cardiac outcomes after randomization for breast cancer therapy. This is reassuring data demonstrating that 25 years after breast radiation, cardiac toxicity does not seem to be responsible for slight decrease in patient survival in the BCT arm. In addition, there was no difference for left- vs. right-sided tumors.

This study was performed in the CT simulation and 3D planning era, therefore reflecting current practice.

Based on this study, in the era of 3D planning, patients with early-stage breast cancer treated with RT do not have a higher risk of long-term cardiac morbidity compared with patients having MRM.

Clinical Implications

This is a unique, important study that assesses multiple laboratory and radiographic aspects of cardiac risk over 25 years after treatment. The results show no increased risk of cardiac risk and they do not explain the slight increased survival seen in the MRM arm of the NCI study. This is reassuring for patients undergoing breast conservation treatment.

One potential limitation is that this study only assessed patients who were alive at 25 years. If they died of cardiac disease prior to this study being performed, they were not included in the analysis. This presents potential bias in the results.

It is important to note that this study was performed in the era of 3D planning. While CT simulation may decrease the risk of heart disease compared to older studies, heart dose and therefore risk is also highly dependent on patient anatomy and physician planning skill.

There have been multiple other studies examining cardiac toxicity that have shown an increased risk of coronary disease with RT.

The UPENN study looked at patients screened with stress tests and cardiac catheterization and found a 10-year risk of CAD: right and left 7% (NS) but a 12-year risk of catheterization-detected abnormalities in the right 8% vs. left 59% (SS), again concluding that left-sided RT increases the risk of coronary damage.

None of these studies, however, had as extensive laboratory and radiographic data as the current study. In addition, they do not report 25 year data. They also do not uniformly use CT planning for the patients treated. For these reasons, the data presented here potentially reflect modern clinical practice the most accurately.

Sep 8, 2011 - Women diagnosed with breast cancer at age 40 or younger have low overall recurrence rates at five and 10 years; and young women with early-stage breast cancer have similar survival rates when treated with breast-conservation therapy or mastectomy, according to two studies presented at the 2011 Breast Cancer Symposium, held from Sept. 8 to 10 in San Francisco.